Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRVRZ4Z)

• DOT Name: Arginine and glutamate-rich protein 1 (ARGLU1)
• Gene Name: ARGLU1
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: ARGL1_HUMAN
• Pfam ID: PF15346
• Sequence:
  MGRSRSRSSSRSKHTKSSKHNKKRSRSRSRSRDKERVRKRSKSRESKRNRRRESRSRSRS
  TNTAVSRRERDRERASSPPDRIDIFGRTVSKRSSLDEKQKREEEEKKAEFERQRKIRQQE
  IEEKLIEEETARRVEELVAKRVEEELEKRKDEIEREVLRRVEEAKRIMEKQLLEELERQR
  QAELAAQKAREEEERAKREELERILEENNRKIAEAQAKLAEEQLRIVEEQRKIHEERMKL
  EQERQRQQKEEQKIILGKGKSRPKLSFSLKTQD
• Function: Required for the estrogen-dependent expression of ESR1 target genes. Can act in cooperation with MED1.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Arginine and glutamate-rich protein 1 (ARGLU1) affects the response to substance of Topotecan.	[20]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Arginine and glutamate-rich protein 1 (ARGLU1).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Arginine and glutamate-rich protein 1 (ARGLU1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Arginine and glutamate-rich protein 1 (ARGLU1).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Arginine and glutamate-rich protein 1 (ARGLU1).	[17]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[11]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Arginine and glutamate-rich protein 1 (ARGLU1).	[19]

References

• [1] Arginine and glutamate-rich 1 (ARGLU1) interacts with mediator subunit 1 (MED1) and is required for estrogen receptor-mediated gene transcription and breast cancer cell growth.J Biol Chem. 2011 May 20;286(20):17746-54. doi: 10.1074/jbc.M110.206029. Epub 2011 Mar 28.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [12] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.